Serum arylhydrocarbon receptor transactivating activity is elevated in type 2 diabetic patients with diabetic nephropathy

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P><P><B>Aims/Introduction</B></P><P>Evidence is emerging that exposure to persistent organic pollutants (POPs) is a risk factor for obesity‐related diseases and for diabetes mellitus (DM). We found that POPs could be measured by a cell‐based arylhydrocarbon receptor (AhR)‐dependent reporter assay. We tested if serum AhR transactivating (AHRT) activities are a risk factor for diabetic nephropathy in people with type 2 diabetes.</P><P><B>Materials and Methods</B></P><P>We enrolled diabetic patients with normoalbuminuria (<I>n </I>= 36), microalbuminuria (<I>n </I>= 29), macroalbuminuria (<I>n </I>= 8) and end‐stage renal disease (<I>n </I>= 31). Sera were tested for their AHRT activities, which were standardized by an AhR ligand, 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) and expressed as TCDD equivalents (TCDDeq pmol/L).</P><P><B>Results</B></P><P>Mean serum AHRT activities were higher in patients with microalbuminuria (40.1 ± 7.1 pmol/L), macroalbuminuria (37.4 ± 5.5 pmol/L) and end‐stage renal disease (59.1 ± 20.0 pmol/L) than in subjects with normoalbuminuria (12.7 ± 5.4 pmol/L; <I>P </I>< 0.05 for all comparisons). Serum AhR ligands showed a correlation with estimated glomerular filtration rate (eGFR;<I> r </I>= −0.663, <I>P </I>< 0.001), serum creatinine level (<I>r </I>= 0.635, <I>P </I>< 0.001), systolic blood pressure (<I>r </I>= 0.223, <I>P </I>= 0.026), glycated hemoglobim (<I>r </I>= 0.339, <I>P </I>< 0.001) and diabetic duration (<I>r </I>= 0.394, <I>P </I>< 0.001). In a multiple regression analysis, diabetic nephropathy was found to be an independent risk factor for higher AHRT activity after controlling for the confounding factors.</P><P><B>Conclusions</B></P><P>The present findings suggest serum AHRT activity, thus serum AhR ligands, is a risk factor for diabetic nephropathy. Further studies are required to clarify if an accumulation of POPs in the body is causally related to diabetic nephropathy.</P>